Artificial Intelligence (AI) is enabling humans to harness vast amounts of data and make breakthrough advances in medicine and the delivery of health services. This is happening across the continuum of needs, service offerings, and care settings. In the world of health and medicine it’s only a matter of time before an adverse event, including death, will arise due to use or reliance on AI-enabled clinical guidance. The complexity of AI technologies has fueled fears that AI systems may cause harm in the face of unforeseen circumstances, or that they can be manipulated to act in harmful ways. AI experiences can have the greatest positive impact when they offer both emotional intelligence and cognitive intelligence, a balance that can improve predictability and comprehension. AI-based personal agents, for example, can exhibit user awareness by confirming and, as necessary, correcting the understanding of the user’s intent. Underlying the principles of reliability, fairness, and security are two fundamental principles: transparency and accountability.